The electrical and mechanical activity of mammalian ventricular muscle is significantly affected by alterations in local pH. Hence, intracellular acidbase control in ventricular muscle is critically important for maintenance of normal heart function. The ionic basis of mammalian ventricular pHi control at pHi greater than 7.1 is unknown and is the focus of this proposal. In many cell types, including cardiac Purkinje cells, pHi recovery from intracellular alkalosis is mediated by Na-independent Cl-H C03 exchange. Our preliminary findings provide strong evidence the exchange is operational in mammalian ventricular cells . The quantitative properties of Na-independent Cl-HCO3 exchange will be examined in this proposal in terms of its pH sensitivity, chloride dependence, contribution to recovery from intracellular alkalosis, sensitivity to inhibitors, and operation in the reverse mode (Cl out: HCO3 in). All experiments will be performed on single ventricular myocytes from adult guinea pigs using a rapid solution switcher and fluorescent indicators for intracellular measurement of H + (SNARF-1) and Cl- (MQAE). The results should provide useful new insight concerning the ionic basis of ventricular pHi control.